The ubiquitin proteasome system in neuropathology

The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis. The UPS facilitates the turnover of proteins in several settings. It targets oxidized, mutant or misfolded proteins for general proteolytic destruction, and allows for the tightly controlled and specific destruction of proteins involved in development and differentiation, cell cycle progression, circadian rhythms, apoptosis, and other biological processes. In neuropathology, alteration of the UPS, or mutations in UPS target proteins may result in signaling abnormalities leading to the initiation or progression of tumors such as astrocytomas, hemangioblastomas, craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of the UPS may also contribute to tumor progression by perturbation of DNA replication and mitotic control mechanisms, leading to genomic instability. In neurodegenerative diseases caused by the expression of mutant proteins, the cellular accumulation of these proteins may overload the UPS, indirectly contributing to the disease process, e.g., sporadic Parkinsonism and prion diseases. In other cases, mutation of UPS components may directly cause pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and muscle and nerve diseases, e.g., inclusion body myopathy and giant axon neuropathy. This paper describes the basic biochemical mechanisms comprising the UPS and reviews both its theoretical and proven involvement in neuropathological diseases. The potential for the UPS as a target of pharmacological therapy is also discussed

V 2 O 5 -ZrO 2 catalyst for selective oxidation of o-xylene to phthalic anhydride: I. Catalyst preparation, catalytic activity and selectivity measurements

The thermal stability, activity and selectivity of a series of V 2 O 5 -ZrO 2 catalyst samples towards o-xylene oxidation to phthalic anhydride have been investigated. It has been established that the phthalic anhydride content yield reaches about 55 mol.% in samples containing 7 and 10 wt.% V 2 O 5 . The selectivity of the catalyst with 7 wt.% V 2 O 5 -ZrO 2 has been compared to that of commercially available V 2 O 5 -TiO 2 (anatase). The investigations have been performed within two temperature ranges. At low temperatures (below 410°C) the V 2 O 5 -TiO 2 (anatase) catalyst shows a better selectivity to phthalic anhydride than the V 2 O 5 -ZrO 2 catalyst does. At high temperatures, the V 2 O 5 -ZrO 2 catalyst is more selective with respect to the main product of partial oxidation due to the positive effect of the ZrO 2 support. Even when the temperature rises up to 550°C and the time of exploitation becomes 50 h, the selectivity of V 2 O 5 -ZrO 2 decreases slightly and remains above 50 mol.%, whereas with the V 2 O 5 -TiO 2 (anatase) sample a significant decrease in selectivity (below 45 mol.%) is observed. The results from experiments on the activity and selectivity of a model mixture of 7 wt.% V 2 O 5 -ZrO 2 and pure ZrO 2 taken in a ratio of 1:1 show that high catalyst selectivity is achieved when the zirconia surface is completely covered by VO x -phases. Studies by different physicochemical analysis methods have shown that V 2 O 5 -ZrO 2 used in a high-temperature regime undergoes no significant phase and structural changes, which is an indication of its good thermal stability. The specific surface area decreases a little, the monoclinic zirconia support exhibits no phase changes and the fine structure of the V 2 O 5 active phase displays no substantial alterations

Trace metal levels in rainbow Trout (Oncorhynchus mykiss) cultured in net cages in a reservoir and evaluation of human health risks from consumption

Although fish consumption has positive health effects, metals accumulated in fish can cause human health risks. In this study, the levels of ten metals in rainbow trout (Oncorhynchus mykiss) farmed in the Keban Dam Reservoir, which has the biggest rainbow trout production capacity in Turkey, were determined and compared with the maximum permissible levels (MPLs). Also, human health risks associated with rainbow trout consumption were assessed. The metal concentrations in rainbow trout were found below the MPLs. The estimated daily intake of each metal was much lower than the respective tolerable daily intake. The target hazard quotient (THQ) for individual metal and total THQ for combined metals did not exceed 1, indicating no health risk for consumers. The cancer risk (CR) value for inorganic arsenic was within the acceptable lifetime risk range of 10(-6) and 10(-4). For carcinogenic and non-carcinogenic effects, the maximum allowable fish consumption rates were high enough to ensure the human health. According to these results, the consumption of rainbow trout farmed in the Keban Dam Reservoir does not pose a risk on human health.This work was supported by Munzur University Scientific Projects Coordination Department (Project Number:YLTUB015-07)